First detection of Leishmania DNA in Lutzomyia longipalpis sensu lato (Diptera: Phlebotominae) in southem Mexico.

Background & objectives: Lutzomyia longipalpis sensu lato is an important vector of Leishmania infantum, the causative agent of visceral leishmaniasis (VL) in Latin America. In Mexico, this species has been recorded in endemic areas of leishmaniasis transmission, but it has never been detected as infected with Leishmania sp. This study aimed to explore the presence of Leishmania DNA in Lutzomyia longipalpis s.l. from samples collected with a human baited trap from an endemic region of leishmaniasis in southeastern Mexico. Methods: This is a prospective study where a total of 45 specimens of Lu. longipalpis s.l. collected in two sites of Yucatan state with records of leishmaniasis were tested. The nuclear ribosomal Internal Transcribed Spacer was amplified for the detection of Leishmania DNA. Results: Two females were positive for Leishmania DNA. None of the specimens positive for parasite DNA were found fed or gravid. Our finding represents the first record of infection by Leishmania in Lu. longipalpis s.l. for the country. Interpretation & conclusion: More studies are necessary to understand the potential role of this vector species in the transmission cycle of the causative agent of leishmaniasis in the southeastern and other regions of Mexico.

Corrigendum: Intrarenal Renin Angiotensin System Imbalance During Postnatal Life Is Associated With Increased Microvascular Density in the Mature Kidney.

[This corrects the article DOI: 10.3389/fphys.2020.01046.].

Intrarenal Renin Angiotensin System Imbalance During Postnatal Life Is Associated With Increased Microvascular Density in the Mature Kidney.

Environmental stress during early life is an important factor that affects the postnatal renal development. We have previously shown that male rats exposed to maternal separation (MatSep), a model of early life stress, are normotensive but display a sex-specific reduced renal function and exacerbated angiotensin II (AngII)-mediated vascular responses as adults. Since optimal AngII levels during postnatal life are required for normal maturation of the kidney, this study was designed to investigate both short- and long-term effect of MatSep on (1) the renal vascular architecture and function, (2) the intrarenal renin-angiotensin system (RAS) components status, and (3) the genome-wide expression of genes in isolated renal vasculature. Renal tissue and plasma were collected from male rats at different postnatal days (P) for intrarenal RAS components mRNA and protein expression measurements at P2, 6, 10, 14, 21, and 90 and microCT analysis at P21 and 90. Although with similar body weight and renal mass trajectories from P2 to P90, MatSep rats displayed decreased renal filtration capacity at P90, while increased microvascular density at both P21 and P90 (p < 0.05). MatSep increased renal expression of renin, and angiotensin type 1 (AT1) and type 2 (AT2) receptors (p < 0.05), but reduced ACE2 mRNA expression and activity from P2-14 compared to controls. However, intrarenal levels of AngII peptide were reduced (p < 0.05) possible due to the increased degradation to AngIII by aminopeptidase A. In isolated renal vasculature from neonates, Enriched Biological Pathways functional clusters (EBPfc) from genes changed by MatSep reported to modulate extracellular structure organization, inflammation, and pro-angiogenic transcription factors. Our data suggest that male neonates exposed to MatSep could display permanent changes in the renal microvascular architecture in response to intrarenal RAS imbalance in the context of the atypical upregulation of angiogenic factors.

Role of Alström syndrome 1 in the regulation of blood pressure and renal function.

Elevated blood pressure (BP) and renal dysfunction are complex traits representing major global health problems. Single nucleotide polymorphisms identified by genome-wide association studies have identified the Alström syndrome 1 (ALMS1) gene locus to render susceptibility for renal dysfunction, hypertension, and chronic kidney disease (CKD). Mutations in the ALMS1 gene in humans causes Alström syndrome, characterized by progressive metabolic alterations including hypertension and CKD. Despite compelling genetic evidence, the underlying biological mechanism by which mutations in the ALMS1 gene lead to the above-mentioned pathophysiology is not understood. We modeled this effect in a KO rat model and showed that ALMS1 genetic deletion leads to hypertension. We demonstrate that the link between ALMS1 and hypertension involves the activation of the renal Na+/K+/2Cl- cotransporter NKCC2, mediated by regulation of its endocytosis. Our findings establish a link between the genetic susceptibility to hypertension, CKD, and the expression of ALMS1 through its role in a salt-reabsorbing tubular segment of the kidney. These data point to ALMS1 as a potentially novel gene involved in BP and renal function regulation.

Vesicle-associated Membrane Protein 3 (VAMP3) Mediates Constitutive Trafficking of the Renal Co-transporter NKCC2 in Thick Ascending Limbs: ROLE IN RENAL FUNCTION AND BLOOD PRESSURE.

Renal cells of the thick ascending limb (TAL) reabsorb NaCl via the apical Na+/K+/2Cl- co-transporter NKCC2. Trafficking of NKCC2 to the apical surface regulates NKCC2-mediated NaCl absorption and blood pressure. The molecular mechanisms by which NKCC2 reaches the apical surface and their role in renal function and maintenance of blood pressure are poorly characterized. Here we report that NKCC2 interacts with the vesicle fusion protein VAMP3, and they co-localize at the TAL apical surface. We observed that silencing VAMP3 in vivo blocks constitutive NKCC2 exocytic delivery, decreasing the amount of NKCC2 at the TAL apical surface. VAMP3 is not required for cAMP-stimulated NKCC2 exocytic delivery. Additionally, genetic deletion of VAMP3 in mice decreased total expression of NKCC2 in the TAL and lowered blood pressure. Consistent with these results, urinary excretion of water and electrolytes was higher in VAMP3 knock-out mice, which produced more diluted urine. We conclude that VAMP3 interacts with NKCC2 and mediates its constitutive exocytic delivery to the apical surface. Additionally, VAMP3 is required for normal NKCC2 expression, renal function, and blood pressure.

Vesicle-associated membrane protein 2 (VAMP2) but Not VAMP3 mediates cAMP-stimulated trafficking of the renal Na+-K+-2Cl- co-transporter NKCC2 in thick ascending limbs.

In the kidney, epithelial cells of the thick ascending limb (TAL) reabsorb NaCl via the apical Na(+)/K(+)/2Cl(-) co-transporter NKCC2. Steady-state surface NKCC2 levels in the apical membrane are maintained by a balance between exocytic delivery, endocytosis, and recycling. cAMP is the second messenger of hormones that enhance NaCl absorption. cAMP stimulates NKCC2 exocytic delivery via protein kinase A (PKA), increasing steady-state surface NKCC2. However, the molecular mechanism involved has not been studied. We found that several members of the SNARE family of membrane fusion proteins are expressed in TALs. Here we report that NKCC2 co-immunoprecipitates with VAMP2 in rat TALs, and they co-localize in discrete domains at the apical surface. cAMP stimulation enhanced VAMP2 exocytic delivery to the plasma membrane of renal cells, and stimulation of PKA enhanced VAMP2-NKCC2 co-immunoprecipitation in TALs. In vivo silencing of VAMP2 but not VAMP3 in TALs blunted cAMP-stimulated steady-state surface NKCC2 expression and completely blocked cAMP-stimulated NKCC2 exocytic delivery. VAMP2 was not involved in constitutive NKCC2 delivery. We concluded that VAMP2 but not VAMP3 selectively mediates cAMP-stimulated NKCC2 exocytic delivery and surface expression in TALs. We also demonstrated that cAMP stimulation enhances VAMP2 exocytosis and promotes VAMP2 interaction with NKCC2.

Renin release: role of SNAREs.

Little is known about the molecular mechanism mediating renin granule exocytosis and the identity of proteins involved. We previously showed that soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNAREs), a family of proteins required for exocytosis, mediate the stimulated release of renin from juxtaglomerular cells. This minireview focuses on the current knowledge of the proteins that facilitate renin-granule exocytosis. We discuss the identity of potential candidates that mediate the signaling and final steps of exocytosis of the renin granule.

Role of the SNARE protein SNAP23 on cAMP-stimulated renin release in mouse juxtaglomerular cells.

Renin, the rate-limiting enzyme in the formation of angiotensin II, is synthesized and stored in granules in juxtaglomerular (JG) cells. Therefore, the controlled mechanism involved in renin release is essential for the regulation of blood pressure. Exocytosis of renin-containing granules is likely involved in renin release; a process stimulated by cAMP. We found that the "soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor" (SNARE) protein VAMP2 mediates cAMP-stimulated renin release and exocytosis in JG cells. To mediate exocytosis, VAMP2 must interact with a synaptosome-associated protein (SNAP). In the renal cortex, the isoform SNAP23 is abundantly expressed. We hypothesized that SNAP23 mediates cAMP-stimulated renin release from primary cultures of mouse JG cells. We found that SNAP23 protein is expressed and colocalized with renin-containing granules in primary cultures of mouse JG cell lysates. Thus, we then tested the involvement of SNAP23 in cAMP-stimulated renin release by transducing JG cells with a dominant-negative SNAP23 construct. In control JG cells transduced with a scrambled sequence, increasing cAMP stimulated renin release from 1.3 ± 0.3 to 5.3 ± 1.2% of renin content. In cells transduced with dominant-negative SNAP23, cAMP increased renin from 1.0 ± 0.1 to 3.0 ± 0.6% of renin content, a 50% blockade. Botulinum toxin E, which cleaves and inactivates SNAP23, reduced cAMP-stimulated renin release by 42 ± 17%. Finally, adenovirus-mediated silencing of SNAP23 significantly blocked cAMP-stimulated renin release by 50 ± 13%. We concluded that the SNARE protein SNAP23 mediates cAMP-stimulated renin release. These data show that renin release is a SNARE-dependent process.

Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP(3) pathway and the ryanodine receptor.

The calcium-sensing receptor (CaSR) is a G-coupled protein expressed in renal juxtaglomerular (JG) cells. Its activation stimulates calcium-mediated decreases in cAMP content and inhibits renin release. The postreceptor pathway for the CaSR in JG cells is unknown. In parathyroids, CaSR acts through G(q) and/or G(i). Activation of G(q) stimulates phospholipase C (PLC), and inositol 1,4,5-trisphosphate (IP(3)), releasing calcium from intracellular stores. G(i) stimulation inhibits cAMP formation. In afferent arterioles, the ryanodine receptor (RyR) enhances release of stored calcium. We hypothesized JG cell CaSR activation inhibits renin via the PLC/IP(3) and also RyR activation, increasing intracellular calcium, suppressing cAMP formation, and inhibiting renin release. Renin release from primary cultures of isolated mouse JG cells (n = 10) was measured. The CaSR agonist cinacalcet decreased renin release 56 ± 7% of control (P < 0.001), while the PLC inhibitor U73122 reversed cinacalcet inhibition of renin (104 ± 11% of control). The IP(3) inhibitor 2-APB also reversed inhibition of renin from 56 ± 6 to 104 ± 11% of control (P < 0.001). JG cells were positively labeled for RyR, and blocking RyR reversed CaSR-mediated inhibition of renin from 61 ± 8 to 118 ± 22% of control (P < 0.01). Combining inhibition of IP(3) and RyR was not additive. G(i) inhibition with pertussis toxin plus cinacalcet did not reverse renin inhibition (65 ± 12 to 41 ± 8% of control, P < 0.001). We conclude stimulating JG cell CaSR activates G(q), initiating the PLC/IP(3) pathway, activating RyR, increasing intracellular calcium, and resulting in calcium-mediated renin inhibition.

Vesicle-associated membrane protein-2 (VAMP2) mediates cAMP-stimulated renin release in mouse juxtaglomerular cells.

Renin is essential for blood pressure control. Renin is stored in granules in juxtaglomerular (JG) cells, located in the pole of the renal afferent arterioles. The second messenger cAMP stimulates renin release. However, it is unclear whether fusion and exocytosis of renin-containing granules is involved. In addition, the role of the fusion proteins, SNAREs (soluble N-ethylmaleimide-sensitive factor attachment proteins), in renin release from JG cells has not been studied. The vesicle SNARE proteins VAMP2 (vesicle associated membrane protein 2) and VAMP3 mediate cAMP-stimulated exocytosis in other endocrine cells. Thus, we hypothesized that VAMP2 and/or -3 mediate cAMP-stimulated renin release from JG cells. By fluorescence-activated cell sorting, we isolated JG cells expressing green fluorescent protein and compared the relative abundance of VAMP2/3 in JG cells versus total mouse kidney mRNA by quantitative PCR. We found that VAMP2 and VAMP3 mRNA are expressed and enriched in JG cells. Confocal imaging of primary cultures of JG cells showed that VAMP2 (but not VAMP3) co-localized with renin-containing granules. Cleavage of VAMP2 and VAMP3 with tetanus toxin blocked cAMP-stimulated renin release from JG cells by ~50% and impaired cAMP-stimulated exocytosis by ~50%, as monitored with FM1-43. Then we specifically knocked down VAMP2 or VAMP3 by adenoviral-mediated delivery of short hairpin silencing RNA. We found that silencing VAMP2 blocked cAMP-induced renin release by ~50%. In contrast, silencing VAMP3 had no effect on basal or cAMP-stimulated renin release. We conclude that VAMP2 and VAMP3 are expressed in JG cells, but only VAMP2 is targeted to renin-containing granules and mediates the stimulatory effect of cAMP on renin exocytosis.

La prevención en salud: posibilidad y realidad / The prevention in health: possibility and reality

INTRODUCCIÓN: Estudios previos evidencian que la prevención de enfermedades aun no está a la altura de las expectativas, sobre todo en lo referente a las acciones de orientación psicológica desarrolladas por profesionales de la salud. OBJETIVO: Reflexionar sobre la necesidad de perfeccionar el quehacer preventivo de los profesionales de la salud. MÉTODOS: Análisis y síntesis de la bibliografía consultada a la luz de investigaciones previas sobre el tema. CONCLUSIONES: Existe una actitud favorable hacia la prevención de enfermedades en los profesionales de la salud, pero requieren de una mayor y mejor preparación en los aportes de las ciencias sociales a las ciencias médicas y de la salud. RECOMENDACIONES: Redefinir el concepto de prevención de enfermedades a la luz de los conocimientos acumulados y las experiencias desarrolladas en las ciencias sociales.

INTRODUCTION: Prior studies demonstrate that disease prevention yet it is not to be worthy of the expectancies, mainly concerning actions of psychological guidances developed by health professionals. OBJECTIVE: To think about the necessity of perfecting the preventive chore of the health professionals. METHODS: To reflect on the need of improve the preventive tasks of health professionals. CONCLUSIONS: In health professionals there is a favorable attitude to diseases prevention, but it is necessary a greater and better training in the social sciences contributions to medical and health sciences. RECOMMENDATIONS: To redefine the concept of prevention of illnesses in the light of the accumulated knowledge and the experiences developed in the Social Sciences.

La prevención en salud: posibilidad y realidad / The prevention in health: possibility and reality

INTRODUCCIÓN: Estudios previos evidencian que la prevención de enfermedades aun no está a la altura de las expectativas, sobre todo en lo referente a las acciones de orientación psicológica desarrolladas por profesionales de la salud. OBJETIVO: Reflexionar sobre la necesidad de perfeccionar el quehacer preventivo de los profesionales de la salud. MÉTODOS: Análisis y síntesis de la bibliografía consultada a la luz de investigaciones previas sobre el tema. CONCLUSIONES: Existe una actitud favorable hacia la prevención de enfermedades en los profesionales de la salud, pero requieren de una mayor y mejor preparación en los aportes de las ciencias sociales a las ciencias médicas y de la salud. RECOMENDACIONES: Redefinir el concepto de prevención de enfermedades a la luz de los conocimientos acumulados y las experiencias desarrolladas en las ciencias sociales(AU)

INTRODUCTION: Prior studies demonstrate that disease prevention yet it is not to be worthy of the expectancies, mainly concerning actions of psychological guidances developed by health professionals. OBJECTIVE: To think about the necessity of perfecting the preventive chore of the health professionals. METHODS: To reflect on the need of improve the preventive tasks of health professionals. CONCLUSIONS: In health professionals there is a favorable attitude to diseases prevention, but it is necessary a greater and better training in the social sciences contributions to medical and health sciences. RECOMMENDATIONS: To redefine the concept of prevention of illnesses in the light of the accumulated knowledge and the experiences developed in the Social Sciences(AU)

Representación social de la prevención de enfermedades en la atención primaria de salud / Social consideration related to diseases prevention in health primary care

INTRODUCCIÓN: el plan del Médico de Familia está instaurado hace más de 20 años para prevenir enfermedades y promover salud; sin embargo, los resultados no se corresponden aún con lo esperado. La forma en que los profesionales de la Atención Primaria de la Salud se representan y practican la prevención pudiera condicionar tal problema. OBJETIVO: explorar la relación de las representaciones sociales del profesional de la salud en la Atención Primaria de la Salud con sus prácticas preventivas cotidianas. MÉTODOS: cualitativos, aplicando las técnicas de entrevista, observación y análisis de contenido a la Revista Cubana de Medicina General Integral. RESULTADOS: los profesionales de la Atención Primaria de la Salud se representan la prevención de enfermedades esencialmente como la ejecución de acciones orientadas por programas e informar a la población sobre las pautas de conducta a seguir. Aunque se manifestó una actitud favorable hacia la prevención en sí, se quejan de sobrecarga laboral y las condiciones de trabajo en este nivel de atención. CONCLUSIONES: las representaciones de la prevención de enfermedades y las prácticas preventivas en Atención Primaria de la Salud son complementarias, puesto que la práctica preventiva en este nivel de atención se caracteriza por realizar lo exigido por los programas, sobre todo, si son priorizados, así como por informar sobre las pautas de conductas preventivas(AU)

INTRODUCTION: family Physician program was established twenty years ago to prevent diseases and to promote the health; however, results are not as expected. How the Health Primary Care professionals consider and practice the prevention could fit such problem. AIM: to explore the relation of social consideration of health professional in Health Primary Care with their daily preventive practices. METHODS: qualitative types applying the interview, observation, and content analysis techniques to Cuban Journal of General Integral Medicine. RESULTS: health primary care professionals consider the disease prevention essentially as the execution of actions directed by programs and the information to population on behavior guidelines to be followed. Although there was a favorable attitude toward the prevention per se, there are complaints of work overload and the work condition at this care level. CONCLUSIONS: considerations of disease prevention and the preventive practices in Health Primary Care are complementary, since the preventive practice at this care level is characterized by that demanded by programs, mainly, if they are priority, as well as to inform on preventive behavior guidelines(AU)

Representación social de la prevención de enfermedades en la atención primaria de salud / Social consideration related to diseases prevention in health primary care

INTRODUCCIÓN: el plan del Médico de Familia está instaurado hace más de 20 años para prevenir enfermedades y promover salud; sin embargo, los resultados no se corresponden aún con lo esperado. La forma en que los profesionales de la Atención Primaria de la Salud se representan y practican la prevención pudiera condicionar tal problema. OBJETIVO: explorar la relación de las representaciones sociales del profesional de la salud en la Atención Primaria de la Salud con sus prácticas preventivas cotidianas. MÉTODOS: cualitativos, aplicando las técnicas de entrevista, observación y análisis de contenido a la Revista Cubana de Medicina General Integral. RESULTADOS: los profesionales de la Atención Primaria de la Salud se representan la prevención de enfermedades esencialmente como la ejecución de acciones orientadas por programas e informar a la población sobre las pautas de conducta a seguir. Aunque se manifestó una actitud favorable hacia la prevención en sí, se quejan de sobrecarga laboral y las condiciones de trabajo en este nivel de atención. CONCLUSIONES: las representaciones de la prevención de enfermedades y las prácticas preventivas en Atención Primaria de la Salud son complementarias, puesto que la práctica preventiva en este nivel de atención se caracteriza por realizar lo exigido por los programas, sobre todo, si son priorizados, así como por informar sobre las pautas de conductas preventivas...

INTRODUCTION: family Physician program was established twenty years ago to prevent diseases and to promote the health; however, results are not as expected. How the Health Primary Care professionals consider and practice the prevention could fit such problem. AIM: to explore the relation of social consideration of health professional in Health Primary Care with their daily preventive practices. METHODS: qualitative types applying the interview, observation, and content analysis techniques to Cuban Journal of General Integral Medicine. RESULTS: health primary care professionals consider the disease prevention essentially as the execution of actions directed by programs and the information to population on behavior guidelines to be followed. Although there was a favorable attitude toward the prevention per se, there are complaints of work overload and the work condition at this care level. CONCLUSIONS: considerations of disease prevention and the preventive practices in Health Primary Care are complementary, since the preventive practice at this care level is characterized by that demanded by programs, mainly, if they are priority, as well as to inform on preventive behavior guidelines...

Lesiones no intencionales en adolescentes de 15 a 19 años / Unintentional injuries in adolescents aged 15-19

Las lesiones no intencionales constituyen importantes causas de mortalidad y morbilidad en Cuba y en el resto del mundo. Con el objetivo de caracterizar estas lesiones en los adolescentes, se realizó un estudio descriptivo en 1 397 estudiantes de Ciudad de La Habana, en el 2005. El cuestionario incluía variables de conocimiento, percepción, actitudes de riesgo y antecedentes de estas lesiones. Se calcularon porcentajes y sus intervalos de confianza al 95 por ciento. La mayoría aceptó que dichas lesiones se podían prevenir, pero solo 13,4 por ciento respondieron correctamente cómo hacerlo. Las vías de información más frecuentes fueron los padres (81,4 por ciento) y la televisión (56,1 por ciento). La mayoría de los adolescentes plantearon que las actitudes de riesgo eran adoptadas por diversión y desconocimiento del peligro; 35,4 por ciento tuvieron antecedentes de estas lesiones. Se concluyó que el conocimiento y la percepción de riesgo insuficientes, junto a las características psicológicas de la edad, favorecieron las prácticas de riesgo.

Unintentional injuries are important causes of mortality and morbidity in Cuba and in the rest of the world. To characterize these injuries in adolescents, a descriptive study was conducted in 1 397 students of Havana City in 2005. The questionnaire included variables of knowledge, perception, risk attitudes, and antecedents of these injuries. Percentages and their confidence intervals at 95 percent were calculated. Most of them accepted that such injuries could be prevented, but only 3,4 percent answered correctly how to do it. The most frequent ways of getting information were parents (81,4 percent) and television (56,1 percent). Most of the adolescents expressed that risk attitudes were adopted as entertainment and due to the lack of knowledge about danger. 35,4 percent had had these injuries. It was concluded that an inadequate knowledge and perception of risk, together with the psychological characteristics of age, favored the risk practices.

Lesiones no intencionales en adolescentes de 15 a 19 años / Unintentional injuries in adolescents aged 15-19

Las lesiones no intencionales constituyen importantes causas de mortalidad y morbilidad en Cuba y en el resto del mundo. Con el objetivo de caracterizar estas lesiones en los adolescentes, se realizó un estudio descriptivo en 1 397 estudiantes de Ciudad de La Habana, en el 2005. El cuestionario incluía variables de conocimiento, percepción, actitudes de riesgo y antecedentes de estas lesiones. Se calcularon porcentajes y sus intervalos de confianza al 95 por ciento. La mayoría aceptó que dichas lesiones se podían prevenir, pero solo 13,4 por ciento respondieron correctamente cómo hacerlo. Las vías de información más frecuentes fueron los padres (81,4 por ciento) y la televisión (56,1 por ciento). La mayoría de los adolescentes plantearon que las actitudes de riesgo eran adoptadas por diversión y desconocimiento del peligro; 35,4 por ciento tuvieron antecedentes de estas lesiones. Se concluyó que el conocimiento y la percepción de riesgo insuficientes, junto a las características psicológicas de la edad, favorecieron las prácticas de riesgo(AU)

Unintentional injuries are important causes of mortality and morbidity in Cuba and in the rest of the world. To characterize these injuries in adolescents, a descriptive study was conducted in 1 397 students of Havana City in 2005. The questionnaire included variables of knowledge, perception, risk attitudes, and antecedents of these injuries. Percentages and their confidence intervals at 95 percent were calculated. Most of them accepted that such injuries could be prevented, but only 3,4 percent answered correctly how to do it. The most frequent ways of getting information were parents (81,4 percent) and television (56,1 percent). Most of the adolescents expressed that risk attitudes were adopted as entertainment and due to the lack of knowledge about danger. 35,4 percent had had these injuries. It was concluded that an inadequate knowledge and perception of risk, together with the psychological characteristics of age, favored the risk practices(AU)

Intervenciones comunitarias contra enfermedades crónicas no transmisibles en el consejo popular “Dragones” / Community-wide interventions against chronic non-communicable diseases in “Dragones” people's council

Antecedentes: las enfermedades crónicas no transmisibles constituyen una las primeras causas de muerte en Cuba. Objetivos: exponer las experiencias más importantes en la ejecución del proyecto “Dragones” llevado a cabo desde el año 1998 hasta el año 2003, para la prevención y control de los factores de riesgo y enfermedades crónicas no transmisibles. Métodos: se realizó una intervención comunitaria basada en dos pilares fundamentales: el fortalecimiento de la atención primaria de salud y la participación activa de la población en el manejo preventivo de las enfermedades crónicas no transmisibles y sus factores de riesgo. Resultados: se apreció una gran recuperación en la calidad de la atención por enfermedades crónicas no transmisibles y sus factores de riesgo entre los años 2000 y 2003. Los aspectos donde se apreció una mayor mejoría fueron la orientación sobre las enfermedades crónicas no transmisibles que padecen los pacientes y los hábitos dietéticos con un aumento de 60,03 % y 50,9 %, respectivamente. Aumentó, también, la realización de prácticas preventivas en el año 2003 y fueron la toma de la tensión arterial y la realización del examen de mama las que alcanzaron mayores porcentajes. Conclusiones: un buen diagnóstico comunitario, la combinación de mensajes bien planificados, la realización de actividades de promoción de salud, la implementación de formas costo-eficaces de intervención y un sistema de vigilancia y evaluación fiables, son los aspectos fundamentales que deben tenerse en cuenta en la ejecución de un programa de intervención comunitaria para la prevención y control de las enfermedades crónicas no transmisibles y sus factores de riesgo.

Background: Chronic non-communicable diseases are one of the first causes of death in Cuba. Objectives: To submit the most important experience in the implementation of “Dragones” project after 5 years of intervention for the prevention and control of risk factors and chronic non-communicable diseases. Methods: A community-wide intervention was performed on two fundamental pillars: the strengthening of primary healthcare and the active participation of the population in preventive management of chronic non-communicable diseases and their risk factors. Results: It was observed that the quality of healthcare to chronic non-communicable diseases and their risk factors from 2000 to 2003 had remarkably increased. The aspects that improved more were counseling on chronic non-communicable diseases that the patients suffered and the dietary habits, with an increase of 60,03 % and 50,9 % respectively. Also, preventive practices increased in number in 2003, being blood pressure measurement and breast screening test the ones that reached higher percentages. Conclusions: A good community diagnosis, combination of well-thought messages, carrying out of health promotion activities, implementation of cost-effective forms of intervention and a reliable system of evaluation and surveillance are the key aspects that should be taken into consideration when implementing a community-based intervention program for the prevention and control of chronic non-communicable diseases and their risk factors.

PGE2-induced hypertrophy of cardiac myocytes involves EP4 receptor-dependent activation of p42/44 MAPK and EGFR transactivation.

Upon induction of cyclooxygenase-2 (COX-2), neonatal ventricular myocytes (VMs) mainly synthesize prostaglandin E2 (PGE2). The biological effects of PGE2 are mediated through four different G protein-coupled receptor (GPCR) subtypes (EP(1-4)). We have previously shown that PGE2 stimulates cAMP production and induces hypertrophy of VMs. Because the EP4 receptor is coupled to adenylate cyclase and increases in cAMP, we hypothesized that PGE2 induces hypertrophic growth of cardiac myocytes through a signaling cascade that involves EP4-cAMP and activation of protein kinase A (PKA). To test this, we used primary cultures of VMs and measured [3H]leucine incorporation into total protein. An EP4 antagonist was able to partially block PGE2 induction of protein synthesis and prevent PGE2-dependent increases in cell surface area and activity of the atrial natriuretic factor promoter, which are two other indicators of hypertrophic growth. Surprisingly, a PKA inhibitor had no effect. In other cell types, G protein-coupled receptor activation has been shown to transactivate the epidermal growth factor receptor (EGFR) and result in p42/44 mitogen-activated protein kinase (MAPK) activation and cell growth. Immunoprecipitation of myocyte lysates demonstrated that the EGFR was rapidly phosphorylated by PGE2 in VMs, and the EP4 antagonist blocked this. In addition, the selective EGFR inhibitor AG-1478 completely blocked PGE2-induced protein synthesis. We also found that PGE2 rapidly phosphorylated p42/44 MAPK, which was inhibited by the EP4 antagonist and by AG-1478. Finally, the p42/44 MAPK inhibitor PD-98053 (25 micromol/l) blocked PGE2-induced protein synthesis. Altogether, we believe these are the first data to suggest that PGE2 induces protein synthesis in cardiac myocytes in part via activation of the EP4 receptor and subsequent activation of p42/44 MAPK. Activation of p42/44 MAPK is independent of the common cAMP-PKA pathway and involves EP4-dependent transactivation of EGFR.

Regulation of the membrane-localized prostaglandin E synthases mPGES-1 and mPGES-2 in cardiac myocytes and fibroblasts.

The proinflammatory mediator cyclooxygenase (COX)-2 and its product PGE(2) are induced in the ischemic heart, contributing to inflammatory cell infiltration, fibroblast proliferation, and cardiac hypertrophy. PGE(2) synthesis coupled to COX-2 involves two membrane-localized PGE synthases, mPGES-1 and mPGES-2; however, it is not clear how these synthases are regulated in cardiac myocytes and fibroblasts. To study this, we used primary cultures of neonatal ventricular myocytes (VM) and fibroblasts (VF) treated with IL-1beta for 24 h. To test for involvement of MAPKs in IL-1beta regulation of mPGES-1 and-2, cells were pretreated with the pharmacological inhibitors of p42/44 MAPK, p38 MAPK, and c-Jun kinase (JNK). mRNA was analyzed by RT-PCR. Protein was analyzed by densitometry of Western blots. mPGES-1 was undetectable in untreated VF but induced by IL-1beta; inhibition of either p42/44 MAPK or JNK, but not p38 MAPK, was almost completely inhibitory. In VM, inhibition of the three MAPKs reduced IL-1beta-stimulated mPGES-1 protein by 70-90%. mPGES-2 was constitutively synthesized in both VM and VF and was not regulated by IL-1beta or MAPKs. Confocal microscopy revealed colocalization of both mPGES-1 and mPGES-2 with COX-2 in the perinuclear area of both VF and VM. Finally, PGE(2) production was higher in VM than VF. Our data show that 1) mPGES-1 is induced in both VF and VM, 2) regulation of mPGES-1 by MAPK family members is different in the two cell types, 3) mPGES-2 is constitutively synthesized in both VM and VF and is not regulated, and 4) mPGES-1 and mPGES-2 are colocalized with COX-2 in both cells. Thus differences in activity of mPGES-1 and COX-2 or coupling of COX-2 with mPGES-1 may contribute to differences in PGE(2) production by myocytes and fibroblasts.